Fourth Ventricular Alloxan Injection Suppresses Pulsatile Luteinizing Hormone Release in Female Rats

Abstract

Abstract. Previous studies have suggested the presence of a glucose-sensing mechanism in the hindbrain that appears to regulate reproductive function as well as feeding behavior. The ependymocytes lining the ventricular wall of the hindbrain showed immunoreactivities to pancreatic glucokinase (GK), a key enzyme for glucose sensing in pancreatic B cells. Our goal in the present study was to test whether the GK-immunopositive ependymocytes in the wall of the fourth cerebroventricle (4V) play a role in regulating gonadal activity. Our approach was to determine the effect of injecting alloxan, a GK inhibitor, into the 4V on pulsatile luteinizing hormone (LH) secretion.Estrogen-primed ovariectomized rats received an injection of alloxan (10 or 20 µg/animal) into the 4V and blood samples were collected every 6 min for 3 h for measurement of blood LH, corticosterone and glucose levels. Pulsatile LH secretion was suppressed after alloxan injection and all pulse parameters were significantly (P<0.05) inhibited by 20 µg alloxan. Plasma corticosterone levels were increased significantly (P<0.05) by 20 µg alloxan, suggesting that LH pulse suppression by alloxan may be at least partly mediated by activation of the hypothalamo-pituitary-adrenal axis. The present results suggest that acute suppression of GK activity in the hindbrain inhibits pulsatile LH secretion in female rats, and supports the idea that GK-immunopositive ependymocytes may sense glucose levels in the cerebrospinal fluid and play a role in regulation of LH secretion. Key words: Alloxan, LH, Glucokinase, Hindbrain, Ependymocytes (J. Reprod. Dev. 50: [279][280][281][282][283][284][285] 2004) t has been well established that reduction of glucose availability inhibits the activity of the hypothalamo-pituitary-gonadal axis in mammalian species [1][2][3]. Pharmacological glucoprivation induced by systemic injection of a glucose antagonist, 2-deoxy-D-glucose (2DG), inhibits estrous cyclicity in female hamsters [1] and rats [4], and pulsatile luteinizing hormone (LH) release in female rats [5]. Glucose availability might monitored by a glucose-sensing mechanism either in the peripheral organs and/or brain to regulate gonadotropin secretion and then reproductive functions.It is now well accepted that glucose-sensing regions are at least partly located in the brain. In addition to several hypothalamic areas, such as the hypothalamic ventromedial, paraventricular and arcuate nuclei and lateral hypothalamic area [6][7][8], the hindbrain has also been suggested as a glucosesensing region, because food intake is increased by 5-thio-D-glucose (5TG) infusion into the fourth cerebroventricle (4V) but not into the third cerebroventricle (3V) in rats with an obstruction of the connection between the 3V and 4V [9]. Feeding is also induced by local application of 5TG into the

Simultaneous Observation of the GnRH Pulse Generator Activity and Plasma Concentrations of Metabolites and Insulin during Fasting and Subsequent Refeeding Periods in Shiba Goats

“…Moreover, the GnRH pulse generator activity is suppressed by the intravenous infusion of 2DG or insulin in goats [25]. These results suggest that change in glucose availability is one of the principal factors involved in the nutritional regulation of the GnRH pulse generator in ruminants as well as in rodents [17,18,32,33]. Further studies will be required to clarify the role of glucose availability in the fasting-induced suppression of GnRH pulse generator activity.…”

Anti-diabetic potentials of Momordica charantia and Andrographis paniculata and their effects on estrous cyclicity of alloxan-induced diabetic rats

“…In fact, diabetes mellitus suppressed luteinizing hormone secretion in streptozocin-induced diabetic rats (Cagampang et al, 1997). In the same manner, alloxan suppressed luteinizing hormone secretion in female rats (Kinoshita et al, 2004). Additionally, diabetic gilts did not exhibit estrous or ovulation (Cox et al, 1994).…”

Food Deprivation Induces Monocarboxylate Transporter 2 Expression in the Brainstem of Female Rat

“…This notion is well consistent with the previous studies revealing the localization of energy-sensing mech- anism in the hindbrain. Fourth ventricular injections of 2-deoxyglucose [14], a glucose antagonist, alloxan [39], a glucokinase inhibitor and mercaptoacetate or trimetazidine [6], inhibitors of fatty acids oxidation, suppresses pulsatile LH release in female rats. Overall, a mechanism sensing energy substrates might be located in the hindbrain of rats.…”